The present invention relates to substituted cinnamic acids and cinnamic acid esters, to a process for their preparation and to their use for synthesizing insecticide precursors.
The synthesis of insecticides is of high importance. Important intermediates in this synthesis are the substituted indanonecarboxylic acid esters and their salts.
WO 95/29171, for example, discloses a process for preparing oxadiazines which are used in the field of crop protection for controlling arthropods. In the multistep preparation process, use is made, inter alia, of substituted indanonecarboxylic acid ester intermediates. The synthesis of the substituted indanonecarboxylic acid esters comprises a Friedel-Crafts reaction of para-substituted phenylacetyl halides with ethylene in the presence of a Lewis acid and an inert solvent with formation of a 2-tetralone of the formula A, where R1 represents F. Cl or C1-C3-fluoroalkoxy, 
the reaction of the compound A with peroxycarboxylic acids with formation of substituted arylpropionic acids of the formula B, 
the esterification of the substituted arylpropionic acids of the formula B with C1-C3-alcohols in the presence of an acid catalyst with formation of the substituted arylpropionic acid esters of the formula C, where Rxe2x80x3 represents C1-C3-alkyl, 
and the reaction of the compounds C with a base with ring closure and formation of the substituted indanonecarboxylic acid ester of the formula D 
This synthesis of the substituted indanonecarboxylic acid esters has the disadvantage that the addition of from 0.9 to 1.5 molar equivalents of a Lewis acid, such as, for example, aluminum trichloride, is required in the Friedel-Craft reaction for the reaction of the phenylacetyl halides with ethylene. As a consequence, large amounts of salts are produced during work-up of the reaction mixture, and thus corresponding volumes of contaminated waste water. Additionally, this synthesis requires the use of peroxycarboxylic acids, such as, for example, peroxyacetic acid, for cleaving the 2-tetralone. For this purpose, the peroxycarboxylic acids have to be employed in an amount of from 2.5 to 3.5 molar equivalents. If the reaction is carried out on an industrial scale, this causes safety risks. Therefore, the reaction temperature has to be exactly maintained and, furthermore, the addition of the peroxycarboxylic acid has to be controlled accurately to avoid an accumulation of excessive amounts of excess peroxycarboxylic acid in the reaction system.
It is furthermore known from J. Pharm. Sci. 67(1) 1978, 81, to prepare the chloro-substituted indanonecarboxylic acid ester 5-chloro-2-methoxycarbonyl-1-indanone starting from 3-chlorobenzaldehyde. Here, 3-chlorobenzaldehyde is initially reacted in pyridine with malonic acid to give 3-chlorocinnamic acid. Following hydrogenation of the ethylenic double bond and cyclization to the 5-chloro-1-indanone, the latter is then reacted with dimethyl carbonate in the presence of sodium hydride and benzene as solvent to give 5-chloro-2-methoxycarbonyl-1-indanone. This synthesis method has the disadvantage of the multistep mechanism which considerably increases the likelihood of the formation of various by-products, which is reflected in only a low yield of 48%. Additionally, the total reaction requires the repeated use of substances such as sodium hydride and benzene, which are expensive, problematic with respect to safety or hazardous to health.
Chemical Abstracts 97, 1982, 109843f discloses 5-bromo-2-carboxy-cinnamic acid which is obtained by oxidative cleavage of 6-bromo-2-naphthol and is then cyclized, reacted with PCl5 and NH3 to give the amide and subsequently, with ring enlargement, reacted in the presence of NaOCI to give 6-bromo-isoquinolin- 1-one.
Also known from Chemical Abstracts 82, 1975, 31200n and 79, 1973, 91891m, is the oxidative cleavage of 6-bromo-2-naphthol with formation of 5-bromo-2-carboxy-cinnamic acid, which leads, via a plurality of steps of amidation, Hoffmann rearrangement and cyclization, to the corresponding substituted indoles.
WO 97/43287 A1 discloses, in a general manner, substituted cinnamic acids and cinnamic acid chlorides which may be substituted on the phenyl ring by a radical R1 and one or two further radicals R2, a large number of meanings being possible for these radicals. Also described is the reaction of the substituted cinnamic acids and cinnamic acid chlorides with other complex starting materials to give specific carboline derivatives which are used as cGMP-PDE inhibitors for cardiovascular indications.
WO 96/04241 A1 discloses, in the form of preparation 45, a cinnamic acid which is substituted in one m-position of the 2-carboxyvinyl radical by methyl carboxylate and in the other m-position by iodine. WO 96/04241 is focused on the preparation of specific, pharmaceutically active benzoylguanidine derivatives, in which the preparation 45 is also used.
EP-A-0 508 264 discloses a process for preparing broadly defined arylolefins which, in a general manner, also include substituted cinnamic acids and cinnamic acid esters. The arylolefins that can be prepared are used in very different areas, for example as optical brighteners, as precursors for optical brighteners, as intermediates for pharmaceutics or as UV absorbers.
Accordingly, it was the object of the present invention to provide intermediates which can be used to synthesize substituted indanonecarboxylic acid esters in a technically simple manner, which does not involve any safety risks.
This object is achieved by substituted cinnamic acids and cinnamic acid esters of the formula (I) 
where X represents F, Cl or J and R1 and R2 are identical or different and represent hydrogen, an optionally substituted C1-C10-alkyl radical or an optionally substituted benzyl radical.
These substituted cinnamic acids or cinnamic acid esters are distinguished by the fact that, for the first time, they allow, in an unexpectedly simple two-step process, a low-cost synthesis of substituted indanonecarboxylic acid esters.
In the substituted cinnamic acids or cinnamic acid esters, X represents F, Cl J, preferably chlorine.
R1 and R2 are identical or different and represent hydrogen, an optionally substituted C1-C10-alkyl radical or an optionally substituted benzyl radical. Preferably, R1 and R2 independently of one another represent hydrogen, methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, tert butyl, n-pentyl, i-pentyl, n-hexyl, i-hexyl, n-heptyl, i-heptyl, n-octyl, i-octyl, n-nonyl, i-nonyl, n-decyl or i-decyl. In particular, R1 and R2 independently of one another represent hydrogen or methyl.
If the C1-C10-alkyl radical is substituted as radical R1 or R2, these substituents can be halogen, hydroxyl or C6-C12-aryl radicals. The benzyl radical as radical R1 or R2 can be substituted by halogen, hydroxyl, C1-C10-alkyl or C6-C12-aryl radicals.
In the cinnamic acids or cinnamic acid esters of the formula (I), the substituent X is preferably in the 5-position to the acrylic acid or acrylic acid ester radical.
Preferred compounds of the formula (I) are methyl 4-chloro-2-(3-methoxy-3-oxo-1-propenyl)benzoate, 4-chloro-2-(3-methoxy-3-oxo-1 -propenyl)-benzoic acid, 4-fluoro-2-(3-methoxy-3-oxo-1-propenyl)benzoic acid, methyl 4-chloro-2-(3-hydroxy-3-oxo-1-propenyl)benzoate or 4-chloro-2-(3-hydroxy-3-oxo-1-propenyl)benzoic acid.
The substituted cinnamic acids or cinnamic acid esters of the formula (I) can be prepared by a variation of the Heck reaction (Process A).
The invention provides a process for preparing the substituted cinnamic acids and cinnamic acid esters of the formula (I) by reacting diazonium salts of the formula (II0 with acrylic acid derivatives of the formula (III) in the presence of a palladium-containing catalyst, where X, R1 and R2 are as defined in formula (I) and A- represents halide, preferably chloride or bromide, sulfate, hydrogen sulfate, nitrate, phosphate, acetate or tetrafluoroborate, characterized in that the reaction is carried out in the absence of bases. This synthesis route is particularly advantageous and thus preferred. 
X, R1 and R2 preferably have the meanings which have also been mentioned as being preferred for the formula (I). A- preferably represents chloride, sulfate, hydrogen sulfate, acetate or tetrafluoroborate.
The reaction principle of this process A is generally known as Matsuda variant of the Heck reaction. According to EP-A-0 584 043, for example, compounds of the formula Arxe2x80x94CHRaxe2x80x94CHRbRc can be prepared in a very general manner, Ra, Rb and Rc independently of one another representing hydrogen or a substituent which is inert to hydrogenation and Ar representing an optionally substituted C6-C20-aryl- or C3-C20-heteroaryl radical. To this end, in a first step, 1 molar equivalent of the diazonium cation Arxe2x80x94N2+ is reacted with at least 1 molar equivalent of a compound CRaxe2x95x90CRbRC with formation of the compound Arxe2x80x94CHRa=CHRbRc, the reaction being carried out in the presence of a catalytic amount of a homogeneous palladium catalyst. Furthermore, addition of a base is a necessary requirement. In particular when the Heck reaction is carried out on an industrial scale, the addition of from 1 to 10 molar equivalents of this base involves additional costs and a complicated work-up of the reaction mixture. In a second step, the compound Arxe2x80x94CHRaxe2x95x90CHRbRc is hydrogenated to give the compound Arxe2x80x94CHRaxe2x80x94CHRbRc. This hydrogenation step is characterized in that the reaction is carried out in the presence of catalytic amounts of a heterogeneous palladium catalyst, which is obtained from the homogeneous palladium catalyst of the first step by reduction prior to the second step.
EP-A-0 584 043 discloses explicitly and especially only those compounds Arxe2x80x94HRaxe2x95x90CHRbRc and Arxe2x80x94CHRaxe2x80x94CHRbRc which carry a sulfonic acid group and optionally other substituents on the aryl radical Ar. However, EP-A-0 584 043 does not disclose the cinnamic acids or cinnamic acid esters of the formula (I) according to the invention which are substituted on the radical Ar=phenyl by a halogen radical and a carboxylic acid or carboxylic acid ester radical, nor their specific preparation according to process A, nor their excellent suitability for use as starting materials for the preparation of substituted indanonecarboxylic acid esters. Compared to the process of EP-A-0 584 043, process A is distinguished by the fact that it is possible to obtain excellent high yields even without the addition of a base, which enhances the economic attraction of the process with respect to work-up and generation of waste water. It is even possible to carry out the process in a solution of mineral or sulfuric acid.
F EP-A-0 508 264, too, discloses the principle of process A, i.e. the preparation, from aryldiazonium salts and olefins in the presence of a palladium catalyst, of the corresponding aryl olefins. However, as in the case of EP-A-0 584 043, the emphasis of EP-A-0 508 264 is placed on compounds which carry a sulfonic acid group on the aryl radical. The selected cinnamic acids or cinnamic acid esters according to the invention and their suitability for preparing substituted indanonecarboxylic acid esters are not explicitly disclosed. According to EP-A-0 508 264, too, in the Heck reaction bases are added and also, favorably, ligands, such as triarylphosphines or bis(diarylphosphine)alkanes capable of forming complexes with the palladium or the palladium salts. In contrast, process A is characterized by the fact that the addition of such auxiliary ligands to the catalyst is usually not required.
The Heck reaction according to variant A is carried out using palladium(II)salts, such as PdCl2, PdBr2, Pd(NO3)2, H2PdCl4, Pd(CH3COO)2, [PdCl4]Na2, [PdCl4]Li2, [PdCl4]K2, or palladium(I) acetylacetonate. PdCl2, Pd(CH3COO)2 and palladium(II) acetylacetonate are particularly preferred. Usually, 0.001-10 mol % of the palladium-containing catalyst, based on the diazonium salt of the formula (II), are employed.
The reaction temperature for variant A should be below the decomposition temperature of the diazonium ion; in general, variant A is carried out at from xe2x88x9220xc2x0 C. to 100xc2x0 C., preferably from 20 to 80xc2x0 C. and in particular from 40 to 65xc2x0 C. The reaction can be carried out with addition of suitable solvents; usually, water, alcohols, preferably methanol, ethanol, propanol, i-propanol or butanol, formic acid, tetrahydrofuran or acetonitrile are added.
The diazonium salts of the formula (II) used in process A are obtainable by reacting halogenated anthranilic acid derivatives with sodium nitrite in acidic aqueous solution or with methyl nitrite in acidic methanol. If sodium nitrite is used, preferably in aqueous solution acidified with sulfuric acid, small amounts of isopropanol may also additionally be present. If methyl nitrite in methanol acidified with sulfuric acid is used, the reaction is generally carried out anhydrous to avoid unnecessary hydrolysis of methyl nitrite. It is advantageous that no organic solvents such as dimethylformamide (DMF), N-methylpyrrolidone (NMP) or dimethyl sulfoxide (DMSO) have to be used in this diazotization. Also advantageous are the low reaction temperatures. The cinnamic acids or cinnamic acid esters of the formula (I) usually precipitate from an aqueous reaction mixture or can be precipitated by additional addition of water. The resulting solids can be dissolved for subsequent reactions by adding organic solvents.
Instead of the diazonium salts of the formula (II), it is also possible to react in the Heck coupling halogenated aromatic compounds of the formula (IV) with the acrylic acid derivatives of the formula (III) (Process B), X, R1 and R2 being as defined for formula (I). Y represents bromine or iodine. EP-A-0 688 757, too, discloses the reaction of such halogenated aromatic compounds with olefins, the palladium catalysts used being specific palladacycles, in particular xcexc-bridged dipalladium complexes. 
The present invention furthermore provides the use of substituted cinnamic acids and cinnamic acid esters of the formula (I) for preparing substituted indanonecarboxylic acid esters of the formula (VII) 
where
X and R2 are as defined for formula (I).
A preferred embodiment of this use is characterized in that the substituted cinnamic acids and cinnamic acid esters of the formula (I) are, in a first step, hydrogenated with hydrogen in the presence of a hydrogenation catalyst, with formation of substituted arylpropionic acids of the formula (VIII), 
which are then, in a second step, cyclized in the presence of a base, with formation of the substituted indanonecarboxylic acid esters of the formula (VIH), where X, R1 and R2 in the formulae (VII) and (VIII) each have the meanings mentioned for the formula (I).
The cinnamic acids or cinnamic acid esters of the formula (I) according to the invention obtained by process A or B can be introduced with or without prior isolation from the respective reaction mixtures into the first step for the synthesis of the substituted indanonecarboxylic acid esters. If, following their preparation by process A or B, the cinnamic acids or cinnamic acid esters of the formula (I) are not isolated, but the entire reaction mixture is used for preparing the indanonecarboxylic acid esters of the formula (VII), the palladium catalyst of the Heck reaction acts as hydrogenation catalyst for the preparation of the arylpropionic acids of the formula (VIII). If the cinnamic acids or cinnamic acid esters are isolated as solids from the reaction mixture of process A or B, a hydrogenation catalyst may be added for the hydrogenation to the arylpropionic acids. However, this is not necessary in all cases if the isolated solid still contains small amounts of the catalyst used in the Heck reaction. If a hydrogenation catalyst is additionally added, it is usually a palladium or platinum catalyst supported on activated carbon.
The hydrogenation to the saturated arylpropionic acids of the formula (VIII) is carried out in the presence of hydrogen and, usually, water, mineral acids and/or alcohols as solvent.
The mineral acid present is usually sulfuric acid, unless the cinnamic acids or cinnamic acid esters are isolated from the reaction mixture of the preceding processes prior to their hydrogenation. The alcohols present can be, for example, methanol, ethanol, propanol, i-propanol or xylol.
The hydrogenation is usually carried out under a pressure of 1-100 bar.
The cyclization of the substituted arylpropionic acids of the formula (VIII) to the corresponding substituted indanonecarboxylic acid esters of the formula (VII) is carried out in the presence of a strong base and a suitable solvent. Usually, the strong base used is an alkali metal hydride, preferably sodium hydride, or an alkali metal alkoxide, preferably sodium alkoxide. Suitable solvents were found to be toluene, xylene, benzene or the alcohols which correspond to the alkali metal alkoxides. In particular, xylene or methanol is used. At a reaction temperature of from 60 to 90xc2x0 C. and a reaction pressure of from 100 to 500 kPa, the reaction time is from 0.5 to 10 hours. Here, the indanonecarboxylic acid esters are obtained as alkali metal salt and are additionally neutralized by addition of an acid, such as, for example, glacial acetic acid or dilute aqueous mineral acid, and then isolated by filtration or extraction. For the reaction conditions of the cyclization of the substituted arylpropionic acids of the formula (VIJI), reference is otherwise made to the corresponding disclosure of WO 95/29 171, which is expressly incorporated herein by way of reference.